文章：

基因甲基化与泌尿生殖系统癌的早期检测：前进的道路

Gene methylation and early detection of genitourinary cancer: the road ahead

原文发布日期：2007-07-01

DOI: 10.1038/nrc2170

类型: Review Article

开放获取: 否

要点：

1. The overall incidence of genitourinary cancer is rising worldwide. Even with prostate-specific antigen (PSA) testing and urine cytology, there is significant benefit to be gained from new methods for the early detection of genitourinary cancer.
2. Aberrant hypermethylation of the promoter region of genes is a frequent and early event in cancer cells. The hypermethylation is associated with loss of function of the gene.
3. Sensitive DNA-methylation-specific PCR technology permits the detection of gene methylation from rare tumour cells in tissue biopsies, urine, blood and other body fluids. Conceptually, the methylation of tumour-suppressor genes is highly specific for neoplastic cells.
4. Key studies have demonstrated sensitive and specific detection of gene methylation in urine from patients with early stage prostate, bladder or renal cancer.
5. Challenges to the clinical implementation of gene methylation-based detection include the need for validation in larger, well-defined populations with optimized and standardized methodology. Further insight into the timing of gene methylation during the earliest stages of neoplastic development will be important.
6. Future directions will probably involve screening with gene methylation for the simultaneous detection, differential diagnosis and prediction of future behaviour of several genitourinary cancer types in a single non-invasive body fluid specimen. Surveillance for the early detection of recurrence will also be a focus of study.

要点翻译：

1. 全球范围内泌尿生殖系统肿瘤的总体发病率正在上升。即使采用前列腺特异性抗原（PSA）检测和尿液细胞学检查，早期检测泌尿生殖系统肿瘤的新方法仍能带来显著益处。
2. 基因启动子区域的异常高甲基化是癌细胞中常见且早期的现象。这种高甲基化与基因功能丧失相关。
3. 灵敏的DNA甲基化特异性PCR技术能够检测组织活检样本、尿液、血液及其他体液中稀有肿瘤细胞的基因甲基化。从概念上讲，肿瘤抑制基因的甲基化对肿瘤细胞具有高度特异性。
4. 关键研究已证明，在早期前列腺癌、膀胱癌或肾癌患者的尿液中能够实现灵敏特异的基因甲基化检测。
5. 基于基因甲基化检测的临床实施面临以下挑战：需要通过优化和标准化的方法，在更大型、特征明确的人群中进行验证。深入理解肿瘤发生最早阶段基因甲基化的时序性也至关重要。
6. 未来方向可能涉及通过基因甲基化筛查，在单一无创体液标本中同时实现多种泌尿生殖系统肿瘤的检测、鉴别诊断及未来行为预测。早期发现复发的监测也将成为研究重点。

英文摘要：

DNA methylation is a common mechanism of inactivation of tumour-suppressor and other cancer genes in neoplastic cells. The advantages of gene methylation as a target for the detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as urine or blood has led to many studies of application in genitourinary cancer. Here, we consider the background, promise and status, challenges and future directions of gene methylation and its clinical utility for the early detection of genitourinary cancer. The challenges of, and strategies for, advancing gene-methylation-based detection are relevant to all types of cancer.

摘要翻译： 

DNA甲基化是肿瘤抑制基因及其他癌症基因在肿瘤细胞中失活的常见机制。基因甲基化作为活检标本及尿液、血液等非侵入性体液中癌症检测与诊断的靶点具有诸多优势，这促使了大量研究将其应用于泌尿生殖系统肿瘤。本文探讨了基因甲基化的背景、前景与现状、面临的挑战及未来方向，以及其在泌尿生殖系统肿瘤早期检测中的临床价值。推动基于基因甲基化检测所面临的挑战与策略，对所有类型肿瘤均具有借鉴意义。

原文链接：

Gene methylation and early detection of genitourinary cancer: the road ahead